Subtle Alterations in Glutamatergic Synapses Underlie the Aging-Related Decline in Hippocampal Function

Excerpt

Aging-related cognitive decline has enormous, tangible costs to national and family health care. The intangible costs are equally detrimental and include decreased quality of life as well as diminished ability to function in and contribute to society. Earlier studies have documented increased difficulties for the elderly on a variety of mental tasks. For example, neuropsychological assessment revealed that after the age of 60, people often have impairments in certain types of memory, particularly recall of recent events (i.e., episodic memory) [1]. A progressive decrease in cognitive ability with advancing age has been well documented not only in humans, but also in rodent models. A clear understanding of the neural changes that accompany aging-related cognitive declines in animal models will aid in the development of strategies to prevent, and therapies to ameliorate, the progression of cognitive decline in the elderly. Although the definition of cognitive function can be broad, including learning and memory, attention, mood, motivation, and planning, the present discussion concentrates on the changes in the cognitive ability most closely associated with the hippocampus. The anatomical, physiological, and biochemical changes in the hippocampus that may contribute to those cognitive abilities also are evaluated.

In this chapter, we will first provide the behavioral evidence characterizing the aging-related decline in performance on hippocampus-dependent tasks in rodent models. We will then consider the aging-related anatomical, physiological, and biochemical changes that occur in the whole hippocampus, as well as in hippocampal subregions. Taken together, the available data suggest that subtle changes in synaptic composition and function, rather than a significant loss of neurons or synapses, are the critical underlying factors for aging-related cognitive decline. The potential for factors such as insulin-like growth factor 1, estrogen, or caloric restriction to impact those aging-related synaptic changes also are considered.